miR-200b-3p antagomir inhibits neuronal apoptosis in oxygen-glucose deprivation (OGD) model through regulating β-TrCP.

Abstract

BACKGROUND:

Hypoxia-ischemic brain damage (HIBD) is a primary cause of morbidity and disability in survivors of preterm infants. We previously discovered that miR-200b-3p plays an important role in HIBD via targeting Slit2. This study was designed to identify novel targets of miR-200b-3p and investigate the relationship between miR-200b-3p and its downstream effectors.

METHODS AND RESULTS:

Cultured primary rat hippocampal neurons were used in the model of oxygen-glucose deprivation (OGD) and RT-qPCR was utilized to detect the alterations of miR-200b-3p in these cells following the OGD. Our study found that the expression of miR-200b-3p was up-regulated in neurons post OGD. Bioinformatics analysis identified that β transducin repeat-containing protein (β-TrCP) is a target gene of miR-200b-3p, and our luciferase reporter gene assay confirmed that miR-200b-3p can interact with β-TrCP mRNA. Hypoxia-ischemic brain damage was induced in three-day-old SD rats and inhibition of miR-200b-3p by injection of antagomir into bilateral lateral ventricles enhanced β-TrCP expression at both the mRNA and protein levels in rats' brains. TUNEL staining and CCK-8 assays found that the survival of hippocampal neurons in the miR-200b-3p antagomir group was improved significantly (p＜0.05), whereas apoptosis of neurons in the miR-200b-3p antagomir group was significantly decreased (p＜0.05), as compared with the OGD group. However, silencing of β-TrCP by β-TrCP siRNA impaired the neuroprotective effect of miR-200b-3p antagomir. H&E staining showed that miR-200b-3p attenuated the pathological changes in the hippocampal region of rats with HIBD.

CONCLUSION:

Our study has demonstrated that β-TrCP is a target gene of miR-200b-3p and that inhibition of miR-200b-3p by antagomir attenuates hypoxia-ischemic brain damage via β-TrCP.

• Authors: Nan Zhang, Lijun Yang, Jialin Wen, Hong Cui
• Journal: Brain research (Brain Res) Vol. 1800 Pg. 148192 (02 01 2023) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 36463959 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Oxygen
• MicroRNAs
• beta-Transducin Repeat-Containing Proteins
• Antagomirs
• Glucose
• RNA, Messenger

Topics

• Infant, Newborn
• Humans
• Rats
• Animals
• Oxygen (metabolism)
• MicroRNAs (metabolism)
• beta-Transducin Repeat-Containing Proteins (pharmacology)
• Antagomirs (pharmacology)
• Rats, Sprague-Dawley
• Glucose (pharmacology)
• Infant, Premature
• Hypoxia-Ischemia, Brain (pathology)
• Apoptosis
• RNA, Messenger